Duodenal and Intestinal Atresia and Stenosis

Etiology

Congenital duodenal obstruction can occur due to an intrinsic or extrinsic lesion. The most common cause of duodenal obstruction is atresia. However, the mechanism that gives rise to duodenal atresia remains unclear. The most well-known hypothesis was proposed by the Viennese anatomist Julius Tandler in 1900. Tandler formulated his hypothesis from his analysis of duodenal development in 11 normal embryos. He observed that as the duodenum progresses through early development, the epithelial lining undergoes a rapid proliferative phase that occludes the lumen of the intestinal tube on day 42 of development. Over the course of the ensuing 2 days, the plug of epithelial tissue develops cracks that give way, reestablishing the continuity of the intestinal lumen ( Fig. 30.1 ).

Tandler stated at the end of his paper on the subject: “If one keeps in mind the fact that on one hand the epithelial occlusion of the duodenum represents a normal event, but on the other hand that it is exactly in this place that most pathologic occlusions of the intestine occur, the question does not appear unjustified to ask whether these processes relate to each other, that is, whether they are causally related. It would not be impossible that in rare cases the physiologic atresia remains and develops into a congenital atresia.”

Over the years, through publication and republication, Tandler’s hypothesis has come to exceed its own status and is frequently presented as fact in the absence of new supporting evidence since he first put forth his hypothesis. Given the lack of clarity on the origins of this defect, it is worthwhile reviewing what is known about how these defects occur. There are two reliable genetic models of duodenal atresia. The homozygous mutation of either the fibroblast growth receptor 2IIIb or its cognate ligand Fgf10 results in duodenal atresias in mouse embryos about 40% of the time. One hundred percent of these embryos also develop type III atresias of the distal colon. Atresias of the duodenum are type III approximately 94% of the time in these murine models, whereas the remaining 6% are type I defects in which there is a luminal interruption in the continuity of the duodenum. The earliest events in this mouse model appear to be an increase in the rate of epithelial apoptosis compared with controls at embryonic day (E) 10.5 that is followed by the absence or attrition of epithelial cells in the proximal loop of the duodenum a full day and a half later at E12.0. Whether the increased apoptosis is a critical event that results in the absence of the epithelium, or whether there are other events such as cell movement, remains unclear. By E12.5, the affected segment of duodenum has narrowed dramatically, and by E13.5 ( Fig. 30.2 ) it has completely disappeared, resulting in the typical type III defect. In contrast to the normal human developmental events in which an epithelial plug forms in the duodenal region from exuberant epithelial growth, the duodenum of the wild-type and mutant mouse embryos never form occlusive epithelial plugs in this anatomic region. Interestingly, the pyloric channel of the wild-type embryos forms a nearly occlusive plug at a later developmental time point: E14.0 ( Fig. 30.3 ), yet pyloric atresias have not been observed in these wild-type mice.

The severity of the defect in this murine model can be shifted by reducing the amount of retinoic acid via a mutation in a single copy of the Retinaldehyde dehydrogenase 2 gene. The addition of this mutation results in the majority of the duodenal atresias manifesting as type I or type II, and only rarely type III defects. What we know from these models is that atresias are associated with the focal loss of epithelial cells as opposed to a hyperproliferative epithelial state that fails to resolve as proposed by Tandler. Also, type I to type III defects represent a continuum of severity arising from a single genetic or molecular mechanism.

There have been isolated reports of specific mutations associated with duodenal atresia in humans. It has been reported in one patient with 17q12 microdeletion, which includes the gene for hepatic nuclear factor β-1. In addition, mutations in transcription factors critical for foregut development have also been implicated. Homozygous mutation of RFX6 , which is critical for normal pancreatic development, has been reported to be associated with duodenal atresia. Mutation in the FoxF1 gene, which is involved in the sonic hedgehog signaling pathway, has also been reported to be associated with duodenal atresia. Interestingly, mouse models in which both copies of this gene are mutated do not manifest intestinal atresias.

With the decreasing cost of complete genomic sequencing, it is likely that mutations in many genes will be found to be associated with duodenal atresia. From there, molecular and cellular mechanisms underpinning this defect will be better delineated. These discoveries may also shed light on one of the more vexing problems in children with intestinal atresias, which is poor intestinal motility. Insights into intestinal motility in this clinical setting may be widely applicable to several unrelated and poorly understood intestinal motility disorders that plague children and adults. Equally important, identification of associated genes will result in screening tools that can diagnose embryos at risk for these defects very early in pregnancy. This will provide an opportunity for early intervention through gene editing. For now, however, the focus of treating this defect will remain on the postnatal surgical interventions required and how we can improve the quality of postoperative management.

Annular pancreas as an etiology for duodenal obstruction warrants special mention, as this form of obstruction is likely due to failure of duodenal development rather than a true constricting external lesion. Thus, the presence of an annular pancreas is simply a visible indication of an underlying atresia or stenosis. Between the fourth and eighth week of gestation, the pancreatic buds merge. In annular pancreas, the tip of the ventral pancreas becomes fixed to the duodenal wall, forming a nondistensible, ring-like or annular portion of pancreatic tissue surrounding the descending part of the duodenum. In annular pancreas associated with duodenal obstruction, the distal biliary tree is often abnormal and may open proximal or distal to the atresia or stenosis. Other reported biliary abnormalities associated with duodenal obstruction include biliary atresia, gallbladder agenesis, stenosis of the common bile duct, choledochal cyst, and immune deficiency.

Classification System

Anatomically, duodenal obstructions are classified as either atresias or stenoses. An incomplete obstruction, due to a fenestrated web or diaphragm, is considered a stenosis. Most stenoses involve the third and/or fourth part of the duodenum. Atresias, or complete obstruction, are further classified into three morphologic types ( Fig. 30.4 ). Type I atresias account for >90% of all duodenal obstructions and contain a luminal diaphragm that includes mucosal and submucosal layers. A diaphragm that has ballooned distally (windsock) is a type I atresia. It is important to understand that the anatomy of the windsock may lead to a portion of the dilated duodenum actually being distal to the actual obstruction ( Fig. 30.5 ). Type II atresias are characterized by a dilated proximal and collapsed distal segment connected by a fibrous cord. Type III atresias have an obvious gap separating the proximal and distal duodenal segments.

More than 50% of affected patients with duodenal atresia have associated congenital anomalies. Approximately 30% are associated with trisomy 21, 30% with isolated cardiac defects, and 25% with other gastrointestinal (GI) anomalies. Approximately 45% of babies are premature, and about one-third exhibit growth retardation.

Pathology

The obstruction can be classified as either preampullary or postampullary, with approximately 85% of obstructions located distal to the ampulla. With complete or almost complete obstruction, the stomach and proximal duodenum become significantly dilated. The pylorus is usually distended and hypertrophic. The bowel distal to the obstruction is collapsed, except in the case of a windsock deformity in which the distal bowel is dilated to a variable length depending on the length of the windsock (see Fig. 30.5 ). In most cases of duodenal obstruction, the GI tract can be decompressed proximally. With complete obstruction of the duodenum, the incidence of polyhydramnios ranges from 32–81%. Growth retardation is also common, presumably from nutritional deprivation from the swallowed amniotic fluid.

Diagnosis

There are multiple benefits to the antenatal diagnosis of duodenal obstruction, including parental counseling. The diagnosis can often be suggested by prenatal ultrasound (US). Sonographic evaluation in fetuses of mothers with a history of polyhydramnios can detect two fluid-filled structures consistent with a double bubble in up to 44% of cases. Despite duodenal obstruction usually occurring by week 12, the reason for failure of early prenatal detection is not entirely clear. Most cases of duodenal atresia are detected between 7 and 8 months of gestation. It is currently believed that immature gastric emptying in utero may contribute to low gastric pressures, failing to dilate the proximal duodenum until later in gestation. While both circular and longitudinal muscle layers are present in the stomach by week 8 of gestation, pressure amplitudes at 25 weeks are only 60% of term gastric pressures.

The presentation of the neonate with duodenal obstruction varies depending on whether the obstruction is complete or incomplete, and the location of the ampulla of Vater in relation to the obstruction. The classic presentation is that of bilious emesis within the first hours of life in an otherwise stable neonate. In about 15% of cases, however, the atresia is preampullary and the emesis is nonbilious. Abdominal distention may or may not be present. In neonates with duodenal atresia, the abdomen is scaphoid. Aspiration via a nasogastric (NG) tube of >20 mL of gastric contents in a newborn suggests intestinal obstruction as the normal aspirate is <5 mL. For patients with stenosis, the diagnosis is often delayed until the neonate has started on enteral feeds and feeding intolerance develops with emesis and gastric distention.

In antenatally suspected cases of duodenal obstruction, as well as in neonates with a clinical presentation consistent with a proximal bowel obstruction, an upright abdominal radiograph is usually sufficient to confirm the diagnosis of duodenal atresia. The diagnostic radiographic presentation of duodenal atresia is that of a double bubble sign with no distal bowel gas ( Fig. 30.6 ). The proximal left-sided bubble represents the air- and fluid-filled stomach while the dilated proximal duodenum represents the second bubble to the baby’s right of midline. In almost all cases of duodenal atresia, the distal bowel is gasless. However, the presence of distal gas does not necessarily exclude the diagnosis of atresia as there is a report of a bifed common bile duct with insertion of one of the ducts proximal and the other distal to the atretic segment, which allowed the air to bypass the atresia. In neonates whose stomach has been decompressed by either NG aspiration or vomiting, 40–60 mL of instilled air into the stomach will reproduce the double bubble. Rarely, the biliary tree is air filled, and a variety of pancreatic and biliary anomalies have been demonstrated ( Fig. 30.7 ). At our institution, neonates who present with bilious emesis and a decompressed stomach on plain abdominal films receive a limited upper GI contrast study to exclude malrotation and volvulus. With duodenal stenosis, a double bubble sign is often not present and the diagnosis is usually made with a contrast study ( Fig. 30.8 ).

Management

After the diagnosis is made, appropriate resuscitation is required with correction of fluid balance and electrolyte abnormalities, in addition to gastric decompression. At our institution, all neonates diagnosed with duodenal obstruction receive a complete metabolic profile, complete blood count, coagulation studies, an abdominal and spinal US, and two-dimensional echocardiography prior to any operation. An emergency operation is performed only in cases where malrotation with concurrent volvulus cannot be excluded.

Prior to the mid-1970s, duodenojejunostomy was the preferred technique for correcting duodenal atresia or stenosis. Since then, the various techniques utilized have included side-to-side duodenoduodenostomy, diamond-shaped duodenoduodenostomy, partial web resection with Heineke–Mikulicz-type duodenoplasty, and tapering duodenoplasty. The long side-to-side duodenoduodenostomy, although effective, is associated with a high incidence of anastomotic dysfunction and prolonged obstruction. Blind-loop syndrome appears to be more common in patients treated with duodenojejunostomy. Gastrojejunostomy should not be performed as it is associated with a high incidence of marginal ulceration and bleeding.

Currently, the preferred technique is either laparoscopic or open duodenoduodenostomy. Originally, a side-to-side anastomosis was performed. A proximal transverse to distal longitudinal (diamond-shaped) anastomosis is now preferred. For the open approach, either a right upper quadrant supraumbilical transverse incision or an umbilical crease incision is utilized. After mobilizing the ascending and transverse colon to the left, the duodenal obstruction is readily exposed. Malrotation should be evaluated at this point as it can occur in association with congenital duodenal obstruction in up to 30% of patients. A sufficient length of duodenum distal to the atresia is mobilized to allow for a tension-free anastomosis. A transverse duodenotomy is made in the anterior wall of the distal portion of the dilated proximal duodenum, and a similar length duodenotomy is made in a vertical orientation on the antimesenteric border of the distal duodenum. The anastomosis is then fashioned by approximating the end of each incision to the appropriate midportion of the other incision ( Fig. 30.9 ). Tapering duodenoplasty is generally not necessary as the proximal duodenal dilation usually resolves after relief of the obstruction. Muscular continuity of the duodenal wall suggests a windsock deformity or diaphragm. This finding should precipitate extra vigilance in the operative correction because the dilated and collapsed bowel are both distal to the windsock, and have been anastomosed in error.

The laparoscopic approach was first described by Rothenberg in 2002. The standard laparoscopic approach begins with the patient supine, and the abdomen is insufflated through the umbilicus. Two other instruments are inserted, one in the baby’s right lower quadrant and one in the right mid-epigastric region, respectively. A liver retractor can be placed in the right or left upper quadrant if necessary. Alternatively, the liver can be elevated by placing a transabdominal wall suture around the falciform ligament and tying it outside the abdomen ( Fig. 30.10 ). The duodenum is mobilized, and the location of obstruction is identified. Using the same principles that have been described for the open approach, a standard diamond-shaped anastomosis is created ( Fig. 30.11 ).

Several studies have compared open and laparoscopic repair of duodenal atresia and have shown that the laparoscopic repair is as safe as the open and highlighted the advantages of early feeding. The historical approach to enteral feeding following duodenal atresia repair involved a period of waiting for the gastric output to become less bilious and the volume of gastric drainage to decrease, indicating return of intestinal function. One study showed that the time spent waiting for the gastric output to decrease is likely not necessary as all of the patients undergoing the laparoscopic duodenoplasty had initiation of feeds without adverse events after an upper GI contrast study on day 5 revealed no leak. When compared with infants undergoing an open operation with the historical postoperative management mentioned previously, there was a marked reduction in hospitalization for the laparoscopically corrected infants, primarily due to the early feeding.

Historically, during repair of duodenal atresia, it has been emphasized that inspecting the entire small bowel to identify a second atresia is important. Given that duodenal atresia and jejunoileal atresia do not share common embryologic etiologies, a multi-institutional review of duodenal atresia patients was undertaken to quantify the incidence of jejunoileal atresia in this population. In this largest series to date, the rate of concomitant jejunoileal atresia in patients with duodenal atresia was <1%. With the low incidence of a concomitant distal atresia, extensive inspection of the entire bowel does not appear necessary.

Early postoperative mortality for duodenal atresia repair has been reported to be as low as 3–5%, with the majority of deaths occurring secondary to complications related to associated congenital abnormalities. Long-term survival approaches 90%. Long-term complications have been noted following repair and include delayed gastric emptying, severe gastroesophageal reflux, bleeding peptic ulcer, megaduodenum, duodenogastric reflux, gastritis, blind-loop syndrome, and intestinal obstruction related to adhesions.

Etiology

Jejunoileal atresia occurs in approximately 1 in 5000 live births. It occurs equally in males and females, and about one in three infants is premature. Although the majority of cases are thought to occur sporadically, familial cases of intestinal atresia have been described. It is generally accepted that jejunoileal atresia occurs as a result of an intrauterine ischemic insult to the midgut, affecting single or multiple segments of the already developed intestine. Intrauterine vascular disruption can lead to ischemic necrosis of the bowel with subsequent resorption of the affected segment or segments ( Fig. 30.12 ).

The hypothesis that most cases of jejunoileal atresia occur secondary to vascular disruption during fetal life is derived from experimental as well as clinical evidence. Isolated mesenteric vascular insults and interference with the segmental blood supply to the small intestine were created in fetal dogs, and resulted in different degrees and patterns of intraluminal obstruction, reproducing the spectrum of stenosis and atresia found in humans. Moreover, the presence of bile, lanugo hair, and squamous epithelial cells from swallowed amniotic fluid distal to an atresia suggests that the atresia occurs subsequent to some event, but that at some time in gestation the intestinal lumen was patent, thus allowing passage of these contents. Additionally, atresias seen in association with other intrauterine vascular insults such as intussusception, midgut volvulus, thromboembolic occlusions, transmesenteric internal hernias, and incarceration or snaring of bowel in an omphalocele or gastroschisis have contributed to wide acceptance of this hypothesis.

The presence of associated extra-abdominal organ abnormalities in jejunoileal atresia is low (<10%) due to its occurrence later in fetal life and the localized nature of the vascular insult. Rarely, jejunoileal atresia has been found in patients with Hirschsprung disease (HD), cystic fibrosis, malrotation, Down syndrome, anorectal and vertebral anomalies, neural tube defects, congenital heart disease, and other GI atresias. Methylene blue, previously used for amniocentesis in twin pregnancies, has been implicated in causing small bowel atresia as well.

Although jejunoileal atresias are usually not hereditary, there is a well-documented autosomal recessive pattern of inheritance of multiple atresias. In these cases, intestinal rotation was normal, mesenteric defects were never observed, and lanugo hairs and squamous cells were not identified distal to the most proximal atresia. All these findings suggest an early intrauterine event. Survival is poor in these infants, even with successful bowel resection.

No correlations have been found between jejunoileal atresia and parental or maternal disease. However, the use of maternal vasoconstrictive medications, as well as maternal cigarette smoking in the first trimester of pregnancy, has been shown to increase the risk of small bowel atresia. Chromosomal abnormalities are seen in fewer than 1% of the babies born with jejunoileal atresia.